Disorders of catecholaminergic neurons have been implicated in a variety of psychiatric diseases, including schizophrenia and affective disorders. The chromaffin cell of the adrenal medulla has proven to be a particularly effective and accessible model for catecholaminergic neurons. Furthermore, the adrenal medulla itself is directly involved in the body's reaction to stress, including anxiety states, and has been implicated in psychopathic behavior. Therefore a better understanding of the biology of catecholaminergic neurons in general, and adrenal chromaffin cells in particular, could provide a better basis for diagnosing and treating some organic psychiatric diseases. The present proposal is to study a basic biological aspect of the chromaffin cell. The chromaffin vesicle within the chromaffin cell is a model for the synaptic vesicle, particularly the adrenergic vesicle. Like other neurosecretory vesicles, chromaffin vesicles contain transmitter, high-energy nucleotides (mostly ATP), and other peptides and proteins. We have observed that in some case, mitochondria are directly connnected to chromaffin vesicles in what we call a mitochondrion-chromaffin vesicle complex. It is possible that ATP may be transfered from the mitochondrion to the vesicle via the complex. In order to test this hypothesis, it is important to first isolate mitochondrion-chromaffic vesicles complexes. A method has recently been devised for isolating rough endoplasmic reticulum-mitochondrial complexes from liver. These complexes are similar in many respects to the complexes we have observed. We are proposing to apply this method, with modification as indicated, to attempt to isolate mitochondrion-chromaffin vesicle complexes. If successful, the complexes will later be characterized and their function studies. This proposed exploratory study is intended to develop a new technique which will be a starting point for future research on a basic problem in neuroscience. It may help explain how high-energy nucleotided are incorporated into neurosecretory vesicles. This in turn may be related to the biological basis of some organic psychiatric diseases.